Michael A E, Pester L A, Curtis P, Shaw R W, Edwards C R, Cooke B A
Department of Biochemistry, Royal Free Hospital School of Medicine, London, UK.
Clin Endocrinol (Oxf). 1993 Jun;38(6):641-4. doi: 10.1111/j.1365-2265.1993.tb02147.x.
The association of adrenal hyperactivity with ovarian dysfunction may involve direct inhibition of ovarian steroidogenesis by glucocorticoids. Therefore, the objectives of this study were to investigate the direct effects of cortisol on luteinizing hormone (LH) action in human granulosa-lutein cells and the modulation of this interaction by ovarian 11 beta-hydroxysteroid dehydrogenase (11 beta HSD).
Effects were investigated in cultured human granulosa-lutein cells isolated from the follicular aspirates of 14 patients undergoing oocyte collection for in-vitro fertilization and embryo transfer.
Pregnenolone production and 3H-cortisol oxidation to 3H-cortisone (11 beta HSD activity) by cultured cells were measured.
In cells from nine (of 14) patients, cortisol inhibited LH-stimulated steroidogenesis in a concentration dependent manner with an ID50 of 1250 +/- SEM 377 nmol/l. In these cultures, the 11 beta HSD activities were high (133 +/- SEM 23 pmol/mg protein/4h) and inhibition of the enzyme with carbenoxolone potentiated the action of cortisol. Conversely, cells from the remaining five patients lacked detectable 11 beta HSD activity and exhibited an increased sensitivity to the inhibitory action of cortisol (ID50 = 158 +/- SEM 41 nmol/l in the absence of carbenoxolone).
Cortisol acts directly in human granulosa-lutein cells to inhibit the support of steroidogenesis by LH and this interaction is modulated by ovarian 11 beta HSD in the majority of patients.
肾上腺功能亢进与卵巢功能障碍之间的关联可能涉及糖皮质激素对卵巢甾体生成的直接抑制作用。因此，本研究的目的是探究皮质醇对人颗粒黄体细胞中促黄体生成素（LH）作用的直接影响，以及卵巢11β - 羟基类固醇脱氢酶（11βHSD）对这种相互作用的调节作用。
从14例接受体外受精和胚胎移植的卵母细胞采集患者的卵泡抽吸物中分离培养人颗粒黄体细胞，研究相关作用。
检测培养细胞中孕烯醇酮的生成以及3H - 皮质醇氧化为3H - 可的松（11βHSD活性）。
在14例患者中的9例患者的细胞中，皮质醇以浓度依赖方式抑制LH刺激的甾体生成，半数抑制浓度（ID50）为1250±标准误377 nmol/L。在这些培养物中，11βHSD活性较高（133±标准误23 pmol/mg蛋白质/4小时），用甘草次酸抑制该酶可增强皮质醇的作用。相反，其余5例患者的细胞缺乏可检测到的11βHSD活性，并且对皮质醇的抑制作用表现出更高的敏感性（在无甘草次酸时ID50 = 158±标准误41 nmol/L）。
皮质醇直接作用于人颗粒黄体细胞，抑制LH对甾体生成的支持作用，并且在大多数患者中，这种相互作用受到卵巢11βHSD的调节。
